Do Probiotics Work?

The word “probiotic” is as general as the word “drug”, so it kind of depends…

By Daniel Sprockett
Illustration by Daniel Gray

This is part two of a four part on series on the significant but largely unknown impact that microbes have on our lives. Read the rest here.

A probiotic is any microbe (most commonly bacteria, but it can also refer to fungi, virus, protozoa, etc.) that helps promote or restore the normal, healthy functioning of your indigenous microbial communities. They’re constantly advertised in print and on television, marketed for adults and children alike, and sold in nearly every chemist’s shop in the country. There are even probiotic-based diet books complete with their own health guru’s. But for all the hype, do probiotics actually work?

The phrasing of the title of this column might lead you to assume that it follows Betteridge’s law of headlines, which states “Any headline which ends in a question mark can be answered by the word ‘no.’” In this case though, the data suggests that the answer is much less definitive. Do probiotics work? Well…it depends.

It depends on what you’re thinking of when you say the word “probiotic.” It all boils down to the difference between what probiotics are in theory, and how most people relate to probiotics in practice.

In theory, probiotics hold enormous potential. Every day, teams of scientists across the globe are discovering new ways in which microbes influence our or diet, our immune system, and even our behaviour. The genetic potential in our genome is essentially permanent at conception, but the genetic potential held in our microbiome, the sum total of all the genes in our indigenous microbiota, remains fluid and mutable throughout our lives. Microbial therapy through probiotics is a tool with which we can tweak our physiology in ways we’d never be able to by targeting our own human cells.

However, in practice, most people inquiring about efficacy of probiotics really just want to know if the little bottles emblazoned with smiling blue blobs are actually worth the money. I’ll just tell you this: the microbial communities that the contents of those bottles purport to improve have been evolving with us for millions of years, and are astoundingly complex. We’ve only begun scratching the surface in terms of identifying these microbes, and know orders of magnitude less about what they’re doing. Most commercial strains of probiotic bacteria were selected based on their ability to remain viable after the manufacturing process and subsequent long-term storage. Few to none of them are major players in the gut microbiome, and those that do survive in the gut normally don’t persist for very long.

Even if a probiotic strain successfully takes up permanent residence in your gut, how would we know if it was actually changing anything for the better? The stated goal of many commercially available probiotics is something akin to restoring balance to your gut ecosystem, but the concept of “balance” is so ill defined that has become scientifically useless. Other claims often sound something like “This product promotes gastrointestinal well-being” or “Clinically prove to help support a healthy immune system!” Such statements are sufficiently vague to render them completely unfalsifiable, which ultimately makes them meaningless. Supplement companies design advertising like this because making a verifiable health claim leaves them vulnerable to litigation and regulation. In 2009, the United States Food and Drug Administration (FDA) threatened legal action if General Mills didn’t stop advertising that their breakfast cereal Cheerios could “lower your cholesterol 4% in six weeks.” As the Wall Street Journal reports:

The FDA said such specific cholesterol-lowering claims can be made only for drugs, and it suggested that if General Mills wants to keep the box labelling as is, it should file a new-drug application for Cheerios.

Probiotics sold over the counter, like Cheerios, are not drugs, and they certainly aren’t regulated like drugs. In fact, the Australian Therapeutic Goods Administration considers probiotics to fall under the auspices of complementary medicine. As far as the Australian government is concerned, commercial probiotics have about as much effect on your health as essential oils and hopelessly diluted homeopathic solutions.

This means that while they must be safe, they are not required to supply any evidence of their effectiveness. This may be in part why Australia hasn’t seen as much backlash against probiotic manufactures as other countries. The European Food Safety Authority recent ruled against allowing probiotic manufacturers to make unsubstantiated health claims. In the US, yoghurt manufacturer Dannon was forced to pay $45 million in a class-action lawsuit stemming from their false claims about the health benefits of their products.

So are all probiotic therapies worthless? No, certainly not. The word “probiotic” is as general as the word “drug.” Probiotics aren’t interchangeable with one another, and like drugs, each needs to be evaluated for efficacy in a specific disease context. Some select forms of microbe therapy have begun undergoing robust clinical testing for particular ailments, and the results have so far been quite promising.

For example, one powerful form of microbial therapy has been helping patients with severe gastrointestinal infections of an especially pernicious germ named Clostridium difficile (C. diff). C. diff infections can cause in severe abdominal pain, relentless diarrhoea, and even death. In recent years, this therapy has been turning heads among scientists and physicians, but it has also begun turning stomachs in the general public, because it involves transplanting faeces from one person into another.

Cartoon by Marc Pearson

Faecal transplants work like this: the gut microbiome of a healthy donor is transferred to the stomach of a critically ill patient via their faeces. The donor stool is first screened for a battery of pathogens, diluted in saline, and delivered to your gut via an enema, colonoscopy, or through a tube threaded down your throat. To reduce the invasiveness of this procedure, researchers have also developed a process where the donor faeces is contained in capsules that can be swallowed whole.

Since the gut microbiome can be conceptualized as a fully functioning organ, this therapy can be viewed of as a type of organ transplant. A study in the New England Journal of Medicine showed that faecal transplant therapy is an extremely effective treatment for C. diff infections, curing 94% of patients. The benefit was so obvious that the study had to end early, so that patients in the control group could undergo faecal transplant therapy as well. Several more articles have now reported similar findings, and a recent meta-analysis placed the overall cure rate around 90%.

We are just now beginning to understand the mechanisms of how faecal transplants work. We’ve known for a while that during an infection, bacterial diversity in the gut plummets while the C. diff population spikes. In this way, C. diff is acting like a weedy invasive species taking over an ecosystem. But how does C. diff force its way into an established community?

Normally, members of your microbiota produce enzymes that free sugars from the mucus layer of your intestinal tract, which they can then consume. These friendly commensal bacteria don’t cause infection, and prevent pathogens from gaining a foothold in the gut. However, following a course of antibiotics, your normal microbiota are greatly reduced, leaving that a pool of available free sugars. Unfortunately, C. diff can consume these sugars very efficiently, and rebound faster than the rest of your microbes. This is why C. diff infections can be difficult to treat with antibiotics. Researchers at Stanford University found that if your commensal microbes don’t have the enzyme that liberates the sugars in the first place, then C. diff can’t gain a foothold. This suggests that one way faecal transplants work is by providing an influx of bacteria to gobble up all of these free sugars before C. diff has a chance to become established. While groups like the US FDA are still deciding how faecal transplants should be regulated, findinsg like this are helping this approach become a more standardized and targeted treatment option.

Evidence-based probiotic therapies hold enormous potential, since they provide new avenues for drug delivery and may persist in the body much longer than most traditional medications. But that doesn’t mean that spending loads of cash on active-culture yoghurts and microbe-laden tablets will have any appreciable effect on your health. Consumers still need to be wary of modern day snake-oil salesmen, especially in the digital realm. One recent survey found that information available online is enormously biased in favour of probiotic manufacturers. Probiotics have also become en vogue among naturopaths and herbalists, since they’re sometimes seen as a more “natural alternative” (…whatever that means). If you have questions about using probiotics to treat a medical condition, please talk to your doctor, or at the very least, your friendly neighbourhood microbiologist.

Daniel Sprockett is a PhD student in the Department of Microbiology and Immunology in the Stanford University School of Medicine in Palo Alto, California, where he studies the ecology of the human microbiome.

Twitter: @DanielSprockett

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